Vitamins

Details

Written by Randy Voyard

Created: 14 February 2008

Vitamins - the Basics

Vit A - Originally called vit A since it was the first one isolated. Later it was called retinol because of the impact it has on vision. As an oil based vitamin it’s stored in the liver (~90% - the rest is in fatty tissue some organs and the eyes). Enough can be stored to meet requirements for several months. It’s main function, aside from night vision, appears to be maintaining and enhancing the protective ability of all linings and coverings. This includes those of organs as well as the exterior skin (via epithelial tissue). It’s also required for cell differentiation during growth and repair, (also formation of antibodies). An effect of deficiency is squamous metaplasia (flattening of cells i.e. mucus lining). in other cases secretions decrease and the cells change to secrete keratin-while becoming hard and dry. If this occurs in the eye, it’s xerophthalmia. The necessary amount of vit A for each individual varies, and high doses can cause toxic reactions. However the recommended intake is ~1000 RE or ~5k i.u. (retinol equivalents-amount of any form of A that functions as 1µg retinol). Carotenes are vit A precursors found in plant pigments (about 50 can be used but there are ~600 known). These carotenoids can be selectively converted into retinoids (retinol, retinal, retinoic acids - each is a form of vit A and has a different function) and have no toxic effects. Beta-carotene is also an antioxidant that can be converted more efficiently than other carotenoids. Pre formed vit A tends to be found in animal sources. Retinoid binders require zinc for transport - low zinc=lo absorption. ~3.3 i.u.=1 RE

Vit B- B1 Thiamine
Two main components were isolated when searching for cure of beriberi. The first was heat resistant and could reduce some symptoms but couldn’t cure. the second component ws destroyed by heat (also air and alkaline conditions) but could cure the disease. Both actually consisted of a number of other substances later identified as the other B vitamins. The cure was labeled B1 -thiamine (~25 other components later identified), and the other was B2 (composed of niacin, riboflavin, B6 and pantothenic acid). This assembly is referred to as the B complex since they tend to be found together in food sources and deficiencies have common elements as well. Though some B vitamins can be made by intestinal flora, it can’t be stored. Antibiotics and diet can affect these bacteria, resulting in increased dietary requirements.

Beriberi is prevalent in a diet of polished rice (or wheat) where the husk, containing bran, is removed. Parboiling before husking helps to preserver the B content. Symptoms for the ‘wet’ form of the disease are: hypertension, heart failure and edema (sound familiar?). The ‘dry’ form (no edema) primarily affects the nervous system (common with POW’s): muscle wasting, nerve degeneration, paralysis, neuropathy, staggering and disorientation, apathy, loss of short term memory. Mandatory enrichment (B1-3 of refined grains (1941) reduced the occurrence of B deficiency diseases. Baking powder and soda, because of their alkalinity destroy thiamine. The use of thiamine in energy pathways means a ready supply is needed for any condition that requires increased cell respiration or conversion of nutrients to glucose. Sugar and alcohol cause depletion (not nutrient dense thus higher demand for vitamin to convert them to glucose), as do certain types of raw fish, and caffeine. Good sources of B complex are the germ and bran of grains, black strap molasses, leafy greens and nutritional yeast. Pork, as opposed to other meats, is a good source of dietary thiamine.

B2 -riboflavin
This one is a bit more stable when exposed to heat, air and acid but not so with light and alkalinity. It is used primarily with oxidative cell metabolism by forming coenzymes (flavins) and enzymes (made with flavins - flavoproteins). These are used to convert B6 and B3 and folic acid into active coenzyme forms as well as amino acid conversions (methionine from homocysteine, tryptophan using niacin), and appears to diminish the ability to use iron for hemoglobin synthesis (via absorption, excretion or metabolism). This implicates the importance of the presence of these nutrients in proportion to each other. Though it is also made in some quantity by intestinal flora, though storage is minimal as with any of the B complex. Dietary intake should be ~1.5 mg/day, but it’s recommended to take ~50 mg (if taken as a supplement) because of loss through digestion.

An isolated deficiency is rare, but symptoms may include sore throat, cheliosis (cracks and wrinkles around the lips), swollen tongue, increased corneal vascularity (light sensitivity). Some studies indicate a potential relationship between B2 levels and both cataract formation (antioxidant activity) and migraines (mitochondrial respiration in brain).

B3- niacin
This B vit was produced back in the late 1800’s by oxidizing the nicotine in tobacco (imported to france by Ct. Nicotin), with the term niacin used in 1942 (nicotinic acid vitamin). It’s resistant to heat, light and air - more so than B1 or 2, and remains stable in acidic or alkaline environments. Tryptophan can be broken down (in the liver) to release the niacin component but it takes ~60 mg to make 1 mg of niacin (protein is 1% tryptophan). This process also requires sufficient amounts of B6, B2 and iron (but tryptophan is also needed to make serotinin). Niacin plays a role as a coenzyme component for ~200 enzymes with functions ranging from macronutrient catabolism (with non-phosphate form) to cell signaling and differentiation. The active phosphate form is involved more with lipid synthesis (fa’s and cholesterol).

Severe deficiency, known as Pellagra (italian-’rough skin’) can cause death. The stages are the four D’s: dermatitis, diarrhea, dementia, death. This became more prevalent as corn became a staple grain in the 1700’s in europe and the 1900’s in the states. The niacin in corn is made bioavailable by soaking or cooking in an alkaline solution (soaking in lime or cooking with ashes), a practice that wasn’t followed with industrial processing and non indigenous cultivators of the grain. Fortification has addressed this problem. Common forms: nicotinamide - also niacinamide- (anti oxidant function - protects insulin secreting B-cells) and nicotinic acid (reduces serum cholesterol, recurrent heart attack, CVA) but pharmacological doses of these can interfere with the activity of other antioxidants (vit E, C, selenium, b-carotene). The nicotinamide form is often used for fortification and supplements, while the acid form is used more for prescription ( over the counter + Rx).

High doses can cause GI upset, hepatitis, hepatotoxicity, flushing, itching, (these tend to occur with nicotinic acid rather than nicotinamide). Recommended ~7 mg/1000 kcal in diet with a min. of ~14-16 mg/day and no more than 35 mg/day for most people.

B6 - pyroxidine
Isolated in 1936 as ‘water soluble B’ and found to play a significant role in fetal development as a coenzyme. It’s involved with single carbon transfers during the synthesis of nucleic acids. There are 3 main forms: pyridoxal, pyridoxine and pyridoxamine. These are all converted to the active form - pyridoxal phosphate (alcohol inhibits this conversion). It is needed as a coenzyme for over 50 enzymes, esp. for synthesis of nonessential amino acids and some neurotransmitters. This is in addition to it’s role in rbc, steroid hormone, and niacin manufacture. With functions as diverse as this, it is fortunate that severe deficiencies are rare (though alcoholics may have a bit of a problem).

Low B6 levels have been associated with higher blood homocysteine levels (and a commensurate increase in cardiovascular disease) and lower lymphocyte production (compromising immune function). Other studies have looked into relationships of B6 levels and carpal tunnel, depression, kidney stones and cognitive function among others.

Recommended levels are ~1.3 - 1.7 mg/day but not more than 100 mg/day, but higher levels of protein intake may require more (since more is needed for amino acid synthesis). If taken in proportion to protein intake it should be ~.16 mg/g protein which is about 2 mg/day in a 2000 kcal diet. Neuropathy may develop with intake over 1000 mg/day. Best sources are meats and whole grains.
B9 - Folate/Folic acid
Can cure anemia (if iron doesn’t help) but not the cns degeneration in cases of pernicious anemia. Original studies noted an improvement in pregnant women with anemia. The symptoms were similar to a B12 deficiency but without the neuro component. Deficiencies of folic acid can lead to birth defects (cleft palate, brain damage) and miscarriage. Isolated in 1945 (from yeast and spinach), it was found to have some functional overlap with B12 esp. with cell replication (rbc’s). It is also needed to metabolize methionine, otherwise homocysteine can accumulate from the conversion. Various forms are found in food but the active form is a coenzyme used to transfer single carbon molecules. Folate is the naturally occurring form but tends to be very unstable when exposed to heat, light and air. Folic acid is the form used to fortify processed foods.

Good sources are liver, yeast, legumes, whole grains. Leafy greens and fresh fruits and veggies also have decent amounts but almost half the content can be destroyed from slicing, cooking and storage of fresh sources. Rec. intake is 3µg/kg, that’s ~200µg(men), 180µg(women), 400µg(pregnant).

B12 - Cobalamin
This particular vitamin is needed in the smallest amounts of any of the B series to prevent a deficiency. It’s also the most complex vitamin molecule and contains a metal (cobalt) ion. One of the active coenzyme forms are used to help convert fa’s and protein for use in the krebs cycle. The other is used in conjunction with folate to make methionine from homocysteine - part of this process regenerates the active form of folate to be used again. B12 is released from food when exposed to the acid and enzymes in the stomach (intrinsic factor or R proteins-secreted by parietal cells of stomach lining). This protein then carries the vitamin into the ileum where they can be separated by the action of the alkaline compounds. The pancreatic enzymes digest the protein and supply calcium to allow the absorption of the B12 by the lining of the sm. intestine. Usually 30-70% of the dietary supply is absorbed this way. If there are problems that compromise this process, absorption rates can drop to 1-3% and injected supplements may be necessary.

Deficiencies can come about from diet, gi tract disease or surgery that impacts the junction of the stomach and sm. intestine and their ability to process and absorb the vitamin. Typical manifestations include pernicious anemia, megaloblastic anemia, and various neurologic symptoms (memory loss, degeneration of cns myelin, dementia).

Sources are non vegetable, requiring supplementation for diets void of animal products. Otherwise shellfish (esp clams and mussels), beef, fish, chicken and dairy are the way to go. Non-animal sources are produced using microorganisms i.e. algae, fermentation (soy tempeh or miso - but B12 content varies). Seaweed may have some of the vitamin but it doesn’t reflect with increased levels in the body when ingested. Bacteria are life forms responsible for actually synthesizing B12. Rec. based on maintaining normal blood concentrations are 2µg daily with no toxicity demonstrated with high dosages (no upper intake level established). Cyanocobalamin and methylcobalamin can both be used to supplement the diet, but the former is most common.
{mospagebreak} C - ascorbic acid
Almost all animals can make vit C except for primates and guinea pigs. Of all the main vitamins, it is the least stable because of it’s reactivity to oxygen (this is also why it’s such a potent antioxidant). Heat and light also reduce its’ potency. This instability also means that it is not found in isolation - it requires the presence of bioflavonoids for transport and assimilation. (some of these compounds have similar and/or assistive functions). It was identified in 1928 by Szent Gyorgyi as the active component of citrus that resolved scurvy. James Lind had earlier recommended english sailors eat such fruits (i.e. limes) as a preventative measure. The prominent signs were bleeding gums and slow wound healing. Other signs of deficiency include tooth decay, bruising, decreased calcium absorption(though high doses can lead to calcium depletion) and susceptibility to infection.

There is further loss of this vitamin when exposed to copper or iron cookware. Sometimes it’s added to foods as an antioxidant to prevent spoilage but also acts as one in the body to protect other vitamins (B1,2, folic acid, A, E) and the cns form oxidative damage. Metabolism of phenylalanine, carnitine and tyrosine as well as the activation of folic acid (into folininc acid) requires C. Erythorbic acid (an isomer of ascorbic acid) is also used for this purpose and though it cant be differentiated when measuring C levels, it doesn’t function as vit C in the body. C functions in a similar fashion to iron in the body, but transports hydroxyl (-OH) instead of O2 to required sites. It increases the bioavailability of iron for sm. intestine absorption and is especially important for synthesis of collagen and a host of other cell secretions (hormones, neurotransmitters-(norepinephrine), bile acids). The replication of DNA requires -OH transport as does the breakdown of toxins. Some studies indicate that increasing intake can reduce blood pressure and cholesterol, with more pronounced effects if it is already deficient.

Vit C is most stable in an acidic environment and doesn’t stay in the blood very long ( most leaves the body in ~3-4 hrs)-normal levels return after ~12 hrs. The body can only hold a certain amount to reach tissue saturation (~5g with concentrations of ~30 mg in adrenals, 200 mg extracellularly) but can only absorb a given quantity regardless of the amount ingested or required. Absorption rates may vary from ~80% or more for <200 mg decreasing to less than 50% with dosages approaching 1g. (400 mg was shown to produce complete tissue saturation). Almost any increase in stress or tissue requirements on the body will increase use of C to counter the oxidative effects: stressors include medications, diuretics, high water intake, toxins, disease and injury. In some studies, very high levels of supplementation (10g/day !) resulted in slight increases of oxalic acid in urine leading some to the conclusion that those with a predisposition to form kidney stones limit their supplementary intake. There are no confirmed side effects with hi doses other than gastric upset (upper limit set at 2g/day)

Sources are predominately fruits and vegetables which complement their vit C content with the presence of bioflavonoids. ~2.5 cups (5 servings) should give ~200 mg with sweet red peppers having one of the highest concentrations (.5 cup raw-141mg vs 1 orange-70mg).
There are a variety of supplement forms of vit C with ascorbic acid being most popular and the synthetic version (L-ascorbic) displaying identical molecular structure and function. There is no significant difference in absorption or function of the various forms though some find the mineral salts (sodium or calcium ascorbate) less irritating to the stomach because of the buffering. What was mentioned about bioflavonoids doesn’t seem to apply when it comes to supplements (freshness counts!). Ascorbyl palmitate (vitamin C ester) is the fat soluble form with one end of the molecule being water soluble. It is used as a preservative for foods like vegetable oils and chips and displays an ability to protect vit E when used in cell membranes. It is also used in topical lotions and creams.

vit D-cholecalciferol (D3)
This vitamin functions like a hormone and is structurally similar to estrogen and cortisone. It is made in the skin (when UV-B radiation passes thru cholesterol type lipids) and affects other organs. Whether manufactured or ingested, it is activated when it passes thru the liver to be hydroxylated then on to the kidneys (becomes calcitriol - active form). The primary functions are the regulation of blood calcium levels (via parathyroid hormones), cell differentiation, and regulation of the immune system. It also plays a role in insulin secretion under certain conditions and blood pressure (by decreasing levels of proteins that induce vessel constriction and sodium and water retention). A drop in calcium levels triggers an increase in pth, which in turn stimulates the activation of more D to increase intestinal calcium absorption (it also does this for phosphorus), reabsorption from the kidneys and eventually, release from bone (caused by 2º hyperparathyroidism). Without sufficient D to maintain calcium levels, the resulting deficiency in this mineral leads to a variety of serious complications esp. for the musculoskeletal system. Severe deficiency results in rickets (in children), osteomalacia (adults), muscle ache and decreased strength.

Fortunately, the body can store enough D in the liver, skin and bone (brain and spleen) to last several months, and it can make ~800,00 i.u. with a days worth of sun exposure. This is how most people maintain their levels and is usually more than sufficient (with the excess stored in the liver for winter months). However, sun exposure will vary according to climate, geography, work schedule etc., so dietary requirements are determined based only on amounts ingested. It is possible to overdose with supplementation, known as hypervitaminosis D. This results in hypercalcemia (high serum levels), and manifests as bone loss (from the Ca/Ph imbalance), kidney stones and soft tissue calcification (esp of the organs). There aren’t enough studies done to determine consistent levels for optimum function, but a conservative max intake level is set at ~2000iu/day (50mcg) even though for most, toxicity isn’t a concern until intake is ~100,000 iu/day.

Dietary sources include animal livers, fatty fish and their oils, and fortified foods including eggs and cereals. There aren’t many food sources, but there are plenty of supplemental products containing combinations of calcium, D and phosphorus or other minerals. Milk is fortified using a synthetic version (D2) made from ergocalciferol (made in yeast - ergosterols instead of cholesterol exposed to sun.)

vit E - alpha tocopherol
RRR - alpha or d -alpha tocopherol is the form actively maintained in the body but gamma tocopherol is the one that predominates in dietary sources. The body tends to breakdown other forms of E except for the alpha and though there is some gamma in the body, its’ specific function is not clear. There are four forms each of these fat soluble tocopherols and tocotrienols (alpha, beta, gamma, delta) and all eight appear to function as antioxidants. E works to protect lipids from oxidation whether bound to lipoproteins (esp. LDL’s-oxidized forms implicated in cardiov dis) or cell membranes. It’s protective effects on the membranes are augmented by the presence of vit C which can also restore ‘oxidized’ E to it’s active form, allowing it to be reused. This is important when cells are exposed to toxic environments. The anti oxidant effects also extend to protecting vit A(also inc. storage and efficient use of it), B, C and saturated fats , Vit E also functions as an anticoagulant by decreasing the ability of platelets to stick and inhibiting the clotting action of vit K. It also impacts the ability of vessel walls to dilate and maintain their integrity while protecting them from peroxide damage

As a fat soluble vitamin, E can be stored in the body (esp liver also adipose tiss, adrenals, pituitary, gonads). It is absorbed into the lymph from the intestines then transported. Once the body os saturated, the excess is excreted thru urine with resolution of any gastric upset that might indicate excessive intake. Increase in dietary intake should be gradual since sudden increases can lead to temporary hypertension. Deficiency is rare but if present, it’s usually because of some problem with absorption or assimilation of dietary fat i.e. cystic fibrosis, liver/gall dysfunction. Not only can these conditions cause a deficiency, prolonged deficiency can also contribute to the development of of these diseases. Sometimes lo fat diets for extended periods may contribute to low serum levels. Although hemolysis (rupture of rbc’s) may be the initial result in cases, it can be followed by neurologic symptoms which can be harder to detect. It can take 10-20 yrs. for symptoms to develop in adults suffering from deficiencies. These include neuropathy, myopathy, ataxia (balance/coordination probs) and visual problems. The nervous systems of premature births are vulnerable to damage and can display symptoms quickly. Capillary structure are particularly vulnerable as well in both adults and infants.

Levels to prevent deficiency symptoms are only about 15-20 mg (22.5-28.5 IU) with an upper limit set at 1000 mg/day alpha tocopherol. More than this can increase the likelihood of capillary leakage or hemorrhage. All forms are absorbed and broken down for elimination while only the alpha form is maintained at substantial levels. Good sources include the germ of grains, various polyunsaturated oils (esp sun and safflower), nuts (esp almonds), spinach and avocado.

Supplement forms of E usually range in amounts from 100-1000 IU of alpha-toco and may include some of the gamma form. RRR (or ‘d’)is the prefix used to denote food source isomers of the vitamin while all-rac (or ‘dl’) is the synthetic form. The latter is composed of all eight isomers of E, but has a lower bioavailability because of the presence of the unusable forms. (for 100IU=67mg d-alpha or 45mg dl-alpha). The ester forms of of E (alpha-tocopheryl succinate or acetate) protect the alpha-t portion from oxidation and can be stored for longer periods while maintaining potency. The alpha-t in these esters has a similar bioavailability to the free form in food.

vit K - ‘ ‘quinones
This fat soluble vitamin occurs naturally either as phylloquinone(K1- made by plants) or menaquinone - n (K2- made by bacteria and found in animal sources, with the ‘n’ representing # of 5 carbon units). It’s primary function is in the process of clot formation where it acts as a coenzyme in the conversion process of glutamic acid. The conversion is what enables calcium to bind to the resulting protein thus allowing the activation of 7 clotting factors (II(prothrombin),VII,IX,X,proteins C,S and Z) which are synthesized in the liver. The mineral binding ability of the vitamin may involve it in the activity of a number of other K dependent proteins. Though the role of these proteins are not yet clear, they include bone mineralization, regulation of soft tissue calcification and cell growth; further research is required before conclusions can be drawn.

A deficiency can result in increased clotting time, nosebleeds, bloody excrement, and easy bruising. Intracranial hemorrhage can result in death for infants, esp. if premature. This has led to the prophylactic administration of vit K for newborns. Problems with liver function or or damage to intestinal flora may lead to deficiencies. The body stores very little and constant resupply is necessary, but the vit K cycle allows a given quantity to be reused a number of times. Anticoagulants i.e. warfarin, function by interrupting the recycling process and producing a constant deficit.

There are no known toxic effects of hi dosages of K1,2 but the impact on clotting means that fluctuations in dietary intake should be avoided for those on anticoagulant medications. Hi levels of vit A and E inhibit vit K activity and antibiotics can impact levels produced by intestinal flora. The actual contribution of intestinal production to overall levels in the body are undetermined (but is less than 50%), as are levels required for adequate function of K dependent proteins. Leafy greens and vegetables are by far the best sources esp. kale, broccoli, and parsley. Unsaturated oils, i.e. soy and canola, also have some quantities but not much (hydrogenation may decrease absorption and bioavailability). Recommended intake levels are ~120mcg/day.